The Study of an Investigational Drug, Revusiran (ALN-TTRSC), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Patients Whose Disease Has Continued to Worsen Following Liver Transplant

ATTR Amyloidosis Clinical Trial

Official title:

An Open-label Study to Evaluate the Efficacy and Safety of Revusiran in Patients With Transthyretin-mediated Familial Amyloidotic Polyneuropathy With Disease Progression Post-Orthotopic Liver Transplant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02595983
• Other study ID #: ALN-TTRSC-005
• Status: Completed
• Phase: Phase 2
• Start date: October 2015
• Est. completion date: February 6, 2017

Study information

• Verified date: March 2019
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate the safety and effectiveness of revusiran (ALN-TTRSC) in adults with transthyretin-mediated amyloidosis (ATTR), whose disease has continued to worsen after liver transplantation. Dosing has been discontinued; patients are being followed-up for safety.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: February 6, 2017
• Est. primary completion date: February 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of FAP (familial amyloidotic polyneuropathy) with documented TTR mutation

• Received an orthotopic liver transplant =12 months before the date of informed consent

• An increase in polyneuropathy disability (PND) score post-transplant

• Polyneuropathy Disability score of =3b

Exclusion Criteria:

• New York Heart Association (NYHA) classification of >2

• Other known causes of sensorimotor or autonomic neuropathy (eg, autoimmune disease)

Related Conditions & MeSH terms

• Amyloid Neuropathies
• Amyloid Neuropathies, Familial
• Amyloidosis
• ATTR Amyloidosis
• Familial Amyloid Neuropathies
• Familial Amyloidotic Polyneuropathy (FAP)
• Polyneuropathies
• Transthyretin (TTR)-Mediated Amyloidosis

Intervention

Drug:
• Revusiran
500mg Revusiran by subcutaneous (sc) injection

Locations

Country	Name	City	State
France	Clinical Trial SIte	Paris
Germany	Clinical Trial SIte	Münster
Portugal	Clinical Trial SIte	Porto
Spain	Clinical Trial SIte	Majorca
Sweden	Clinical Trial Site	Umea
United Kingdom	Clinical Trial SIte	London

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

France,  Germany,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage Change From Baseline in Serum TTR at Month 6	A negative percentage change from baseline at Month 6 indicates a reduction in serum TTR level.	Month 6
Secondary	Percentage Change From Baseline in Serum TTR Over 18 Months	A negative percentage change from baseline indicates a reduction in serum TTR level.	Weeks 3, 7, 12, 18, 24, 26 (Month 6), 39 (Month 9), 52 (Month 12), 57, 78 (Month 18)
Secondary	Change From Baseline in Modified Neurological Impairment Score (mNIS +7) Composite Score Over 18 Months	The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome. A negative change from baseline indicates an improvement.	Baseline, Months 6, 12, 18
Secondary	Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Score	The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.	Baseline, Months 6, 12, 18
Secondary	Number of Participants in Each Polyneuropathy Disability (PND) Stage Based on Worst Post-Baseline Score	PND Scores: Stage 0: No symptoms, Stage 1: Sensory disturbances but preserved walking capabilities, Stage 2: Impaired walking capacity, but ability to walk without a stick or crutches, Stage 3A/B: Walking with help of 1 or 2 sticks or crutches, Stage 4: confined to wheel chair. For each stage (0-4) at baseline, the number of participants is presented at their worst post-baseline score for each stage (0-4) post-baseline. Worst post-baseline is defined the highest PND classification for a participant recorded after the first dose of study drug.	Baseline, Months 6, 12, 18